Cisplatin (cis-[PtCl2(NH3)2]) is one of the most widely used platinum (Pt) based therapeutic anticancer drugs. Such Pt (II) compounds do, however, exhibit severe side effects due to their indiscriminate and uncontrollable cytotoxic effects which include nausea, neurotoxicity and renal toxicity. The drug is believed to exert its cytotoxicity through binding DNA, particularly to adjacent GG bases. Additional disadvantages of Pt (II) based drugs are associated with their intravenous administration route, which requires increased medical attention and often results in additional complications and discomfort for the patient than would be the case if oral administration was possible. Another problem frequently associated with the use of cisplatin is the acquired resistance of tumour cells to the drug following an initial treatment.
Such disadvantages have prompted the search for alternative and improved anticancer drugs and therapies. Presently clinical trials are underway using oral administration of Pt (IV) compounds such as the Johnson-Matthey compound JM216. Pt (IV) compounds are substantially inert to substitution and can act as a good precursor for highly reactive Pt (I) compounds, which readily undergo substitution. Ideally, such conversion of Pt (IV) to Pt (II) would occur at the target side of the tumour in a controlled manner. The presently available Pt (IV) compounds are, however, thought to be reduced to active Pt (II) species in the blood and, hence, are also accompanied by the adverse side effects of indiscriminate cytotoxicity associated with cisplatin. Blood plasma is particularly rich in powerful reducing agents such as glutathione (GSH), cysteine, and ascorbate, whereby, once administered to the body, Pt (IV) compounds are vulnerable to reduction and activation.
Another anti-cancer strategy which has been used, namely photodynamic therapy, entails irradiation with visible or near-infrared light to generate, highly reactive and cytotoxic, singlet oxygen species via porphyrin mediated conversion of triplet oxygen. Advances in lasers and fibre optics have enabled more or less highly localised delivery of the light to tumours of epithelial origin. Such targeted cytotoxicity is highly desirable in the treatment of tumours and there is a need for a compound which is substantially stable both ex vivo, and in vivo after administration, but is activatable to a cytotoxic form in a spatially and temporally controlled manner whilst being substantially non-toxic and physiologically acceptable prior to activation, and it is an object of the present invention to provide such a compound.